pro-siRNA for Highly Potent and Cost-effective RNAi Therapeutics

RNA interference, mediated by small interfering RNAs (siRNAs), is an important gene regulatory mechanism in eukaryotes. Synthetic siRNAs have become an indispensable tool for research and RNAi therapeutics are being developed to target disease-associated genes and viruses. siRNA medicines could revolutionise the drug discovery process because they are easy to design and can target any gene including previously undruggable proteins. However synthetic siRNAs are expensive and there are limitations in delivery. Dr. Linfeng Huang invented the world’s first and only cell-based method of making siRNAs in bacteria (published in Nature Biotechnology and patented by Boston Children’s Hospital). Bacteria made siRNAs, named pro-siRNAs for prokaryotic siRNAs, are highly efficient and specific in silencing genes in human cell lines. pro-siRNAs, which are easy to produce, could solve the high cost problem of siRNA drugs. This project aims to perfect the pro-siRNA technology to facilitate its commercialisation. We will create a patentable and optimal method for large-scale production of pro-siRNAs using bacterial fermentation that can be readily adopted by an industrial partner. We will also explore the use of pro-siRNAs as RNAi therapeutics for lung cancer, delivered by a multifunctional and targeted nanoparticle drug delivery system.